A fatal case of mitochondrial DNA depletion syndrome with novel compound heterozygous variants in the deoxyguanosine kinase gene

摘要

The deoxyguanosine kinase (DGUOK) gene controls mitochondrial DNA (mtDNA) maintenance, and variation in the gene can alter or abolish the anabolism of mitochondrial deoxyribonucleotides. A Chinese female infant, whose symptoms included weight stagnation, jaundice, hypoglycemia, coagulation disorders, abnormal liver function, and multiple abnormal signals in the brain, died at about 10 months old. Genetic testing revealed a compound heterozygote of alleles c.128T>C (p.I43T) and c.313C>T (p.R105^*) of the DGUOK gene. c.128T>C (p.I43T) is a novel variant located in exon 1 () in the first beta sheet of DGUOK. Her mother was an allele c.313C>T (p.R105^*) heterozygote, which is located in DGUOK exon 2 () between the third and fourth alpha helixes. c.313C>T (p.R105^*) is predicted to result in a 173 amino acid residue truncation at the C terminus of DGUOK. There are as many as 112 infantile mtDNA depletion syndrome (MDS) cases in the literature related to DGUOK gene variants. These variants include missense mutations, nucleotide deletion, nucleotide insertion, and nucleotide duplication. Integrated data showed that mutations affected both conserved and non-conserved DGUOK amino acids and are associated with patient deaths.